DESCRIPTION (Adapted from the application): Electrically enhanced transdermal delivery of calcitonin has the potential to be a superior alternative to patient injection for several clinical indications. Iontophoresis, alone or in combination with electrophoration, could deliver calcitonin for chronic treatment of post-menopausal osteoporosis and Paget's disease, possibly via a biofeedback system and under certain circumstances electroporation followed by iontophoresis could deliver calcitonin rapidly for control of hypercalcemic emergencies. The goal of this proposal is to establish the optimum combination of electrical parameters such as ionophoretic current density, electroporative voltage, pulse length, number and spacing to rapidly achieve steady state flux of therapeutically relevant concentrations of calcitonin for various indications. Formulation factors such as pH, buffer, ionic strength, and the use of excipients such as stabilizers, preservatives and/or protease inhibitors will also be optimized. After establishing the optimum formulation and electrical protocol by in vitro studies across human epidermis, results will be validated in hairless rats by measuring serum calcitonin levels as well as blood calcium levels in the rat. This proposed study will expand on the most encouraging preliminary results which have shown a 4 fold enhancement in the flux of calcitonin transported across human skin in vitro when iontophoresis was combined with electroporation over iontophoresis alone. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE